Improvement in health/science literacy tops the nation's health/education agenda, meshing with NIH-NIAID's strategies to energize the clinical research enterprise, enhance public understanding of science [specifically ~ Infection (In) and Immunity (Im)], and expedite translation of discovery into practice. This R25 proposal, from an experienced team led by accomplished clinician-scientists devoted to outcomes-oriented educational interventions targeting diverse/disadvantaged K-16 and health professional students, builds on a national infrastructure of people, programs, and partnerships as well as student cyberliteracy. Using our web-based Virtual Clinical Research Center and Questionarium (an interactive Questioning Space)(VCRC/Q) launched in 2011, specific aims are: 1) connect, customize, and scale this unique one stop learning grid (for integrating and personalizing domain-specific content, learning activities, and user services) to deliver a new In/Im curriculum and provide state-of-the-art multifaceted bidirectional linkage between the biomedical world and K-12 schools and general public; 2) develop a new inquiry-driven student-centered multimedia K-12 core curriculum - Infection and Immunity: Knowns and Unknowns (Answers! and Questions?) (InIm K!/U?). InIm K!/U? targets diverse/disadvantaged Arizona high school students, then age-adapted for K-8, on VCRC/Q or face-to-face for classroom, laboratory, and home use. It introduces the language (vocabulary) of medicine and highlights the spectrum of NIAID-related basic, clinical, and translational research topics, tools, and scientist role models mixing diverse experts and multilevel students as presenters/ producers. The innovative theme and learning strategy interweaves biomedical Knowledge (today's Knowns/Answers!) and Ignorance (Unknowns/Questions? - future learning and discovery), mirroring authentic science and encouraging students to ask their own questions and explore answers in VCRC/Q, classrooms/school labs, and home. Among topics introduced in animated graphically attractive teaser/snapshot form at the K9-12 then K-8 level will be: introductory mini-overview of pathobiology (inflammation, necrosis, immunity and neoplasia); research tools; bacterial, fungal, and viral organisms; infections including tuberculosis, sexually transmitted diseases, coccidioidomycosis, AIDS, influenza; MRSA, wound/surgical infections; parasitic diseases from worms and insect vectors; 1 and 2 immune disorders, organ transplantation; vaccines; and bioterrorism; 3) provide K-12 teacher training and support through serial interactive multimedia teacher workshops, year round inservice consultation, and online social networking to encourage teacher and student ownership/innovation reflecting state/national standards. Comprehensive formative/summative evaluation includes 3-phases (design, implement, disseminate) and short- and long-term assessment of program and teacher/student participant outcomes including as questioners. National/ international dissemination centers in VCRC/Q's expanding multimedia, multidisciplinary, multi-institutional partnerships and social networking to enhance impact.